Deep Brain Stimulation of the Nucleus Accumbens in Severe Enduring Anorexia Nervosa: A Pilot Study

Abstract

IntroductionAnorexia nervosa (AN) is one of the most debilitating psychiatric disorders, becoming severe and enduring in a third of cases; with few effective treatments. Deep brain stimulation is a reversible, adjustable neurosurgical procedure that has been gaining ground in psychiatry as a treatment for depression and obsessive–compulsive disorder, yet few studies have investigated AN. Abnormal eating behavior and the compulsive pursuit of thinness in AN is, in part, a consequence of dysfunction in reward circuitry and the nucleus accumbens (NAcc) is central to reward processing.MethodsPhase 1 prospective open-label pilot study of seven individuals with severe enduring AN. Electrodes were implanted bilaterally into the NAcc with stimulation at the anterior limb of the internal capsule using rechargeable implantable pulse generators. The protocol of 15 months included 12 months of deep brain stimulation incorporating two consecutive, randomized blind on-off fortnights 9 months after stimulation onset. The primary objectives were to investigate safety and feasibility, together with changes in eating disorder psychopathology.ResultsFeasibility and safety was demonstrated with no serious adverse events due to deep brain stimulation. Three patients responded to treatment [defined as > 35% reduction in Eating Disorders Examination (EDE) score at 12 months] and four patients were non-responders. Responders had a statistically significant mean reduction in EDE scores (50.3% reduction; 95% CI 2.6–98.2%), Clinical Impairment Assessment (45.6% reduction; 95% CI 7.4–83.7%). Responders also had a statistically significant mean reduction in Hamilton Depression Scale, Hamilton Anxiety Scale and Snaith-Hamilton pleasure scale. There were no statistically significant changes in Body Mass Index, Yale-Brown-Cornell Eating Disorder Scale, Yale-Brown Obsessive–Compulsive Scale and World Health Organization Quality of Life Psychological subscale.ConclusionThis study provides some preliminary indication that deep brain stimulation to the NAcc. Might potentially improve some key features of enduring AN. In this small study, the three responders had comorbid obsessive-compulsive disorder which predated AN diagnosis. Future studies should aim to further elucidate predictors of outcome.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [Project ID 128658].

Inclusion of the severe and enduring anorexia nervosa phenotype in genetics research: a scoping review

“…In the selection of a subset of participants from the Anorexia Nervosa Genetics Initiative (ANGI) to include in their assessment of the polygenic association of severity and long-term outcome in AN, Johansson et al [ 50 ] included in their criteria for the severe enduring subtype a ≥ 5 year follow-up time, defined by the authors as years between initial registration and ANGI recruitment. Finally, in two of the three studies evaluating the effectiveness of deep brain stimulation, an illness duration of ≥ 10 years was required for participant inclusion [ 51 , 52 ], with the third requiring > 7 years [ 53 ]. Case study, clinical trial and study participants included in groups indicated as manifesting a severe and enduring phenotype tended to have illness of longer duration.…”

“… Does not propose criteria Does not propose criteria Does not propose criteria Does not propose criteria 29. [ 53 ] Scaife et al, 2022 Study evaluating efficacy of DBS in those with SE-AN Deep brain stimulation of the nucleus accumbens in severe enduring anorexia nervosa: A pilot study. Inclusion criteria:>13, < 16 Inclusion criteria:>7 Inclusion criteria: ≥3 voluntary intensive treatments (partial or full hospitalization) and ≥2 trials of psychological treatment Various tools used though not to define SE-AN 30.…”

Neuromodulation of Eating Disorders: A Review of Underlying Neural Network Activity and Neuromodulatory Treatments

“…In our review, we identified multiple studies assessing the efficacy of DBS for the treatment of AN. While there exists variability in results, with some studies reporting a stable BMI [ 101 , 114 , 116 ], the vast majority reported improvements in BMI, with none reporting a decline ( Table 3 ). Notably, we did not identify studies utilizing DBS for the treatment of BN, representing a potential future direction for investigation.…”

“…Additionally, it should be noted that while most studies reported significant weight restoration and improvement in ratings of comorbid symptoms (i.e., depression, OCD, and anxiety), QoL improvement is less certain. Most studies did not provide strict metrics for QoL, although it is worth noting that among those that did [ 103 , 106 , 116 , 117 ], all but De Vloo et al found improvements in such measures [ 115 ]. In reference to their findings, De Vloo et al suggested that an early post-operative placebo effect and expectation bias could contribute to more positive short-term results which diminish in the long term [ 115 ].…”

Neural effects of deep brain stimulation on reward and loss anticipation and food viewing in anorexia nervosa: a pilot study

“…Studies on DBS in AN have explored diverse targets including the subcallosal cingulate cortex (SCC), nucleus accumbens (NAcc) and ventral anterior limb of the internal capsule (vALIC) [ 1 , 3 – 6 ]. Interestingly, different targets have shown comparable clinical effects, suggesting that DBS is effective at different targets and normalizes wider aberrant network activity in the brain.…”